t(2;12)(p12;p13) IGK/CCND2
t(12;14)(p13;q32) IGH/CCND2
t(12;22)(p13;q11) IGL/CCND2

2009-12-01   Jean-Loup Huret  

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

Mantle cell lymphoma (MCL)

Note

This review does not include a case of t(2;12)(p12;p13) found in myeloid malignancy (Lai et al., 1995), a case of acute lymphoblastic leukemia with a t(12;14)(p13;q32) and IgH/ETV6 involvement (Lu et al., 2002); five cases of t(12;22)(p13;q11), not herein included either, have also been described in lymphoid malignancies, but with an unknown CCND2 status (see Mitelman database). Finally, there are a number of chronic myeloid leukemia aberrant translocations with t(12;22), which again represent other diseases.

Phenotype stem cell origin

The cases of mantle cell lymphomas with the above translocations were typical mantle cell cases, with CD5+, CD20+, CD10-, CD23- expression, except for the lack of CCND1 expression.

Epidemiology

Five cases are available: 4 cases of MCL (Gesk et al., 2006; Herens et al., 2008; Wlodarska et al., 2008), and a case of chronic lymphocytic leukemia (CLL) transforming into a Richter disease (Qian et al., 1999).

Clinics

The patients are in stage IV of the disease, with a nodular, or nodular/diffuse pattern. There was 3 male and 2 female patients, aged 33, 52, 65, 70, and ? years.

Prognosis

Data is missing in most cases; the two patients with data on prognosis died: the patient with Richter disease, and a MCL case, who died 64 months after diagnosis.

Cytogenetics

Cytogenetics morphological

There was two cases of t(2;12), one case of cryptic t(12;14), one case of t(12;22), and one case with no metaphase.

Additional anomalies

+3 was found in two cases, +21 in one case, a complex karyotype in one case, and +12 and a t(14;19)(q32;q13) in the CLL/Richter case.

Genes Involved and Proteins

Note
IgH, IgK, or IgL can be alternative partners of CCND2.
Gene name
CCND2 (cyclin D2)
Location
12p13.32
Protein description
CCND2 promotes cell cycle progression at the G1/S start transition. Interacts with CDK4 and CDK6. CCND2 is activated through B-cell antigen receptor-induced, and CD19-induced signal transduction pathways, including the RAS/RAF/MAPK pathway, the PLC gamma pathway, and the IKK/NF-KB pathway. CCND2 is critical in B-cell development (review in Chiles, 2004).

Result of the Chromosomal Anomaly

Oncogenesis

Overexpression of cyclin D2.

Highly cited references

Pubmed IDYearTitleCitations
183910762008Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas.27

Article Bibliography

Pubmed IDLast YearTitleAuthors
153221452004Regulation and function of cyclin D2 in B lymphocyte subsets.Chiles TC et al
168613582006A chromosomal translocation in cyclin D1-negative/cyclin D2-positive mantle cell lymphoma fuses the CCND2 gene to the IGK locus.Gesk S et al
182231792008Cyclin D1-negative mantle cell lymphoma with cryptic t(12;14)(p13;q32) and cyclin D2 overexpression.Herens C et al
78850351995Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoïesis and a high incidence of P53 mutations.Lai JL et al
123999652002The utility of spectral karyotyping in the cytogenetic analysis of newly diagnosed pediatric acute lymphoblastic leukemia.Lu XY et al
104606091999Cyclin D2 promoter disrupted by t(12;22)(p13;q11.2) during transformation of chronic lymphocytic leukaemia to non-Hodgkin's lymphoma.Qian L et al
183910762008Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas.Wlodarska I et al

Summary

Fusion gene

IGH/CCND2 IGH (14q32.33) CCND2 (12p13.32) M t(12;14)(p13;q32)

Note

Mantle cell lymphoma are usually associated with a t(11;14)(q13;q32), a CCND1/IgH rearrangement, and cyclin D1 overexpression.
Atlas Image
t(12;22)(p13;q11) IGL/CCND2 R-banded karyotype (left) and FISH using dual color break apart probe CCND2 (12p13) (Empire genomics) (right) - Courtesy Karolien Beel, Peter Meeus, Geneviu00e8ve Ameye and Lucienne Michaux

Citation

Jean-Loup Huret

t(2;12)(p12;p13) IGK/CCND2
t(12;14)(p13;q32) IGH/CCND2
t(12;22)(p13;q11) IGL/CCND2

Atlas Genet Cytogenet Oncol Haematol. 2009-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1487/gene-fusions-explorer/img/cancer-prone-explorer/